Radiotherapy-induced gut toxicity: Involvement of matrix metalloproteinases and the intestinal microvasculature

Abstract

Purpose To review the literature surrounding the involvement of the endothelium and matrix metalloproteinases (MMP) in radiotherapy-induced gut toxicity (RIGT) and further elucidate its complex pathobiology.

Results RIGT involves damage to the gastrointestinal mucosa and is associated with diarrhoea, pain, and rectal bleeding depending on the area of exposure. The mechanisms underpinning RIGT are complex and have not yet been elucidated. Members of the MMP family, particularly MMP-2 and -9, have recently been identified as being key markers in RIGT and chemotherapy-induced gut toxicity (CIGT). Furthermore, the microvasculature has long been implicated in the development of toxicities following both chemotherapy and radiotherapy, however, the mechanisms behind this are yet to be explored.

Conclusions It is proposed that matrix metalloproteinases are key regulators of endothelial mediators, and may play a key role in inducing damage to intestinal microvasculature following radiotherapy.

Keywords:

• Mucositis
• radiotherapy
• metalloproteinases
• endothelium
• gastrointestinal

Acknowledgements

R.L.S is the recipient of an Australian Postgraduate Award. N.A.-D. is the recipient of a Clinical Centre of Research Excellence Post- Doctoral Training Fellowship.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.